Only a fraction of the enormous potential of ionizing radiation has been described and understood at molecular and genetic levels, and much of our understanding has not yet been harnessed in modern medicine. We are proposing to acquire a new preclinical irradiator to fulfill the need of multiple peer-reviewed funded users, including eleven NIH-funded investigators who are pioneering a new understanding and new applications for ionizing radiation. This community has developed over the past decade at New York University School of Medicine (NYU). Since the establishment of the Department of Radiation Oncology in 2000, a widespread recognition of the multi-dimensional uses of radiation as a tool for research and treatment has occurred. The department has developed collaborations with existing NYU scientists and recruited an outstanding group of new investigators who are at the forefront of understanding the molecular and genetic mechanisms by which ionizing radiation acts on normal and cancer tissues, and affects the normal and cancer tissue micro-environment. At the molecular level, major research areas of the faculty that would benefit and depend on a new irradiator include ionizing radiation alteration of DNA repair, mRNA transcription, mRNA stability, mRNA translation, and protein stability. In addition to more classical radiobiology research, NYU has explored less conventional uses of radiotherapy, such as its capacity to induce "danger signals" to influence the immune system. Original research at the detailed cytokine and immune cell level, with a focus on its applications to stimulate anti-tumor immunological responses, has been pioneered. Currently fourteen distinct teams of investigators from twelve distinct departments are conducting preclinical, translational and basic research on ionizing radiation. The experimental Co60 unit designated in 2000 for animal work has been recently de-commissioned because it is impossible to repair the operating system. To sustain the continuity of NIH-funded research projects and other federally funded projects, a clinical linear accelerator, a Varian Clinac 2100MV (which is also used for patients) has been assigned for after-hours use. Unfortunately, this relegates research studies to evening and late night hours, resulting in increased administrative and overtime operational costs. Moreover, it is not possible to conduct low dose and long duration studies with the Clinac, because of the technical specifications of the equipment. A new experimental irradiator will assure greater productivity and encourage investigators to pursue hypothesis-driven research on the effects and applications of ionizing radiation. A Theratronics Gammabeam X200 (GBX200) Co60 research irradiator is requested, to be installed in our current experimental vault, after removal of the current out-of service machine. The new equipment is essential for maintaining ongoing radiation research programs. NYU SoM is poised to marshal extraordinary research and clinical breadth and expertise to become a pioneering world leader in radiation biology medical research.